Coates 2017.
Study characteristics | ||
Methods | Single‐centre RCT Conducted: Oregon Reproductive Medicine Center Enrolment: December 2013‐August 2015 Power calculation: stated Randomisation: stratified block randomisation sequence was prepared by a professional third party (sealedenvelope.com). The allocation sequence was stratified for female age (< 35, 35–37, 38–40, and 41–42 years) and number of prior ART cycles (%2 or R3). Timing of randomisation: at time of hCG administration (trigger) Nature of intervention: day‐6 embryo cryopreservation by means of vitrification. Follow‐up: LBR after the first ET |
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Participants | 179 women (91 freeze‐all, 88 control) Inclusion criteria:
Exclusion criteria: the need to use surgically retrieved sperm (microsurgical epididymal sperm aspiration (MESA) or testicular sperm aspiration (TESA)), women using preimplantation genetic diagnosis for a single‐gene or chromosomal disorder, egg donor cycles, gender selection cycles, decreased ovarian reserve indicated by early follicular phase serum FSH level > 10 IU/L or random serum AMH level < 1 ng/mL, and any medical reasons occurring before recruitment that would not allow a participant to undergo a fresh ET such as the need for uterine surgery before transfer. |
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Interventions | Assisted hatching was performed on all embryos on day 3 after retrieval. The embryos were transferred back to culture media until day 5 or day 6 of development. Embryos were biopsied for PGS on day 5 or 6, based on the development of the hatching process. women had either 1 or 2 embryos transferred depending on availability of euploid embryos and woman's request. Women assigned to the conventional strategy received 1 or 2 fresh embryos on day 6, any remaining embryos were frozen. In the FET group, there was no fresh transfer and available embryos had been cryopreserved on day 6 by means vitrification. In menstrual cycles following the ovum pick‐up the endometrium was artificially prepared for transfer using estradiol and progesterone for transfer of a maximum of 2 embryos. |
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Outcomes | The primary outcomes were: implantation rates (number of gestational sacs divided by the number of embryos transferred per group), ongoing pregnancy rates (defined as a pregnancy beyond 8 weeks), and LBR after the first ET. No prespecified secondary outcomes were stated in the manuscript. In the trial registration the following secondary outcome was stated: determining retrospectively if mitochondrial DNA content is linked to implantation potential and if that is measurable by NGS. |
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Notes | Funding: supported by Life Technologies, Carlsbad, CA; Oregon Reproductive Medicine, Portland; and Reprogenetics, NJ We requested additional information regarding cumulative data from the authors by email but we did not receive a response. |
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Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Stratified block randomisation sequence was prepared by a professional third party (sealedenvelope.com). |
Allocation concealment (selection bias) | Unclear risk | No information provided |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | Blinding of doctors and participants was not possible due to the nature of the intervention. |
Blinding of outcome assessment (detection bias) All outcomes | Low risk | Outcome assessor blinding was not reported, however primary outcome is not likely to be influenced by lack of blinding. |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Data were analysed for all randomised women. |
Selective reporting (reporting bias) | Unclear risk | Not all registered outcomes were reported (correlation of mitochondrial DNA and implantation) Not all reported outcomes were registered (ongoing pregnancy rates, and LBR after the first ET) Study was registered in a prospective trials register with the trial number: NCT02000349. |
Other bias | Unclear risk | 3 of the authors disclosed to be co‐owner of Oregon Reproductive Medicine. 2 of the authors reported to be founding partner for Reprogenetics. (Cumulative) data per subsequent menstrual or cryo‐transfer cycle not reported (relevant for time‐to‐pregnancy comparison and the related comparison of results after first transfer in FET group vs results after first 2 transfers in fresh group). |